This proposal is based on the hypothesis that the neuroregulatory control of the episodic secretion of growth hormone is governed by brain somatostatin and the monoamines, norepinephrine and serotonin. In order to test this hypothesis, the major objectives of this investigation are to define the projections of somatostatin neurons in hypothalamic and extrahypothalamic regions and explore the functional roles and possible interactions of somatostatin and monoamines in the regulation of growth hormone secretion in the adult male rat. The experimentation required will employ microdissection of individual brain nuclei, highly sensitive methods for quantitation of biogenic amines, somatostatin and growth hormone, selective neurotoxins for catecholaminergic and serotoninergic systems, and chronic cannulation techniques that permit longitudinal studies for assessment of the effects of a given experimental procedure of pulsatile growth hormone secretion. Specifically, the aims of the project are: l) To continue the biochemical mapping of the axonal projection pathways of somatostatin-containing neurons in the forebrain, 2) To determine the role of central somatostatin, norepinephrine, and serotonin systems in the regulation of episodic growth hormone secretion in unanesthetized, freely-behaving adult male rats, 3) To evaluate the role of central somatostatin system in stress-induced suppression of pulsatile growth hormone release, and 4) To examine the effects of selective noradrenergic and serotoninergic denervations of brain regions on somatostatin in hypothalamic and extra-hypothalamic sites. Definition of the somatostatinergic pathways should help clarify the role of inhibitory inputs to the medial basal hypothalamus that are important to maintain phasic inhibition of growth hormone. Observations on the effects of monoamines and somatostatin on growth hormone should lead to the elucidation of basic control mechanisms controlling growth hormnone and permit a more rational diagnostic and therapeutic approach to disorders of growth hormone segrotion.